Highlights From the 75th Annual Meeting of the American Thyroid Association

Kenneth D. Burman, MD

Disclosures

November 07, 2003

In This Article

Graves' Ophthalmopathy

Graves' ophthalmopathy is noted clinically in perhaps 10% to 20% of patients with Graves' disease, although its presence is more common when radiologic images are used for evaluation. The clinical manifestations of Graves' ophthalmopathy can vary from mild to severe, and may include burning, itching, discomfort, diplopia, redness, and, rarely, visual loss. Graves' ophthalmopathy can present prior to, during, or following the diagnosis and treatment of Graves' hyperthyroidism, although most frequently the diseases present within about 12-18 months of each other. The cause of Graves' ophthalmopathy is not known, but it likely relates to the presence of thyroid-stimulating hormone (TSH) receptor antibodies that bind not only to the thyroid gland but probably also to retro-ocular tissues such as adipose tissue. This binding results in stimulation and proliferation of the adipocytes, which then causes enhanced cellular proliferation and the production of mucopolysaccharides and enlargement of the orbital space. T cells are also activated and secrete cytokines that contribute to the clinical findings. At the 2003 American Thyroid Association Annual Meeting, there were several presentations that discussed Graves' ophthalmopathy.

The treatment of Graves' ophthalmopathy has been problematic. In mild cases, local eye drops and eye care are sufficient. However, in more severe cases, additional therapies, such as corticosteroids and/or external radiation, may be beneficial. Kendall-Taylor and colleagues[1] performed a double-blind, placebo-controlled trial assessing the effectiveness of octreotide long-acting repeatable (LAR) therapy. Fifty euthyroid subjects with active ophthalmopathy received either octreotide LAR (30 mg) or placebo for 16 weeks, and then both groups received 30 mg octreotide LAR for an additional 24 weeks. Specific objective parameters assessing clinical activity score, soft-tissue inflammation, and diplopia were performed. During the initial 16 weeks, the octreotide LAR-treated patients had significant improvement in their ophthalmic index compared with placebo-treated subjects. There was no further difference in the second treatment interval. Overall, all parameters tended to improve with octreotide LAR as compared with controls, but improvement with treatment was found to be statistically significant only for exophthalmos. In summary, octreotide LAR may be potentially beneficial in selected patients with Graves' ophthalmopathy, but the improvement was modest.

Another controversial issue regarding the treatment of Graves' ophthalmopathy is the potential benefit of removing or ablating as much thyroid tissue as possible. The rationale underlying this possible effect is that TSH receptor antibodies mediate, at least to some extent, the development and progression of the ophthalmopathy. The continued presence of thyroid tissue supplies a persistent antigenic stimulation for the presence of TSH receptor antibodies. Menconi and colleagues[2] randomized 81 Graves' disease patients with moderate ophthalmopathy into 1 of 3 groups: treatment with methimazole, near-total thyroidectomy, or near-total thyroidectomy plus 131-I therapy. Proptosis, eyelid width, clinical activity, and diplopia were examined at 6 and 12 months. Although these results are to be considered preliminary, diplopia and eyelid width improved in patients receiving a thyroidectomy. These authors concluded that compared with methimazole alone, thyroidectomy appeared to be beneficial and appeared to improve the course of ophthalmopathy after steroid therapy. This study did not assess the potential benefits of 131-I therapy alone.

Given these 2 studies, where do we stand with regard to the diagnosis and treatment of Graves' ophthalmopathy? The basic principles still apply. That is, evaluation and treatment of these patients using an experienced, integrated team approach that allows for patient input are essential. In this context, mild ophthalmopathy is treated with local measures. More severe ophthalmopathy can be treated with the judicious use of steroids and, in some instances when these measures are ineffective, external radiation. It is usually important to treat the hyperthyroidism with definitive therapy such as 131-I (and, rarely, thyroid surgery). There may be transient exacerbation of ophthalmopathy after 131-I therapy, which can be ameliorated with adjunctive steroid use.

These 2 abstracts, however, give us additional information. If the above-noted measures are inadequate or unsuccessful, it may be worthwhile to utilize long-acting octreotide for a period of time. (It should be noted that this agent is not approved for this indication by the US Food and Drug Administration.) Most patients with ophthalmopathy should have definitive therapy, either 131-I treatment to induce permanent hypothyroidism or, more rarely, a thyroidectomy. The Menconi abstract gives further credence to the importance of lowering the thyroid antigen load to the greatest extent possible as a major aspect of treatment for Graves' ophthalmopathy. I suspect that 131-I will be just as useful as surgery was shown to be in the abstract noted.

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